Development of novel diagnostics and antibody-drug-conjugates using a combination of click chemistry and enzymatic ligation.

Host: Professor Elizabeth Gardiner

Abstract:

Recombinant antibodies currently attract the majority of pharmaceutical research and development investment and therapeutic success can be seen in various areas of medicine. Progress in diagnostic imaging is driven by the application of antibodies for molecular and functional imaging using various modalities. Nanomedicine plays an increasing role in the development of antibody diagnostics as well as therapy because of the potential for increased payload of both contrast agents and therapeutic molecules.

An ideal example demonstrating the potential of antibody-targeted nanomedicine are single-chain antibodies (scFvs) directed against the integrin αIIbβ3. These scFvs are not only targeting an epitope that is specific for platelets but also to the activated form of the αIIbβ3 receptor thereby providing unprecedented specificity towards activated platelets. This allows the development of diagnostic approaches for the detection of thrombosis or emboli as well as many inflammatory processes in which platelets are involved such as atherosclerotic plaque instability and ischemia reperfusion injury.

We have developed several generally usable approaches to couple various tracers and nanoparticles to these scFvs. These approaches include genetic, biological (e.g. sortase coupling) and chemical (e.g. click chemistry) approaches. The coupled products include various effector molecules, contrast reagents, radiotracers as well as particles such as liposomes, ultrasound microbubbles, iron beads, micelles and layer-by-layer particles. For imaging we used various modalities such as ultrasound, MRI, PET/CT and fluorescence imaging.

In conclusion, antibody targeted nanoparticles hold great promise to provide major advances in various fields of diagnostic imaging as well as therapeutic targeting, including the combination of both in personalised theranostic approaches.

Biography:

Prof Hagemeyer is a Senior Research Fellow of the NHMRC and Head of the NanoBiotechnology Laboratory at the Australian Centre for Blood Diseases (Monash University). He is also the acting Director of Monash Biomedical Imaging, one of the largest imaging facility in Australia. He studied Chemistry in Germany and obtained a PhD in Biochemistry from the University of Freiburg (Germany). He made contributions to the field of Cytochrome P450 metabolism in the brain before moving into cardiovascular research developing anti-thrombotic fusion proteins and novel imaging probes. He has particular expertise in the use of small recombinant single-chain antibodies for molecular imaging and drug delivery. His main current research theme is the development of "bio-better" antibodies with added functionality using the novel Sortase Bio Click technology developed in his laboratory. He has published widely in leading journals (Circ Res, Adv Mater, Angew Chem..) on vascular biology, recombinant antibodies and nanotechnology and has been supported throughout his career by national and international fellowships and grants.